Reduction of carbonyl compounds constitutes a very important technology in various fields, for example in the production of drug intermediates. As the so far known practical methods of reducing carbonyl compounds, there may be mentioned the Meerwein-Ponndorf-Varley reduction (MPV reduction) and the reduction using diisobutylaluminum hydride (DIBAH).
The MPV reduction is a method of reducing carbonyl compounds using an aluminum trialkoxide, such as Al(O-iPr).sub.3, as a reducing agent or reduction catalyst. This method is in frequent use as an economical method of reducing various ketones and aldehydes, since the aluminum trialkoxide used there and the alcohol such as isopropyl alcohol are inexpensive [Organic Reactions, volume 2, page 178 (1944)].
However, the MPV reduction, which uses an aluminum trialkoxide, has problems. The progress of the reaction tends to be very slow at low reaction temperatures mainly because of the low reactivity of said reagent. For increasing the reaction rate and the yield, a high reaction temperature not lower than 50.degree. C., for example, is required. Said reduction is thus unsuited for the reduction of unstable carbonyl compounds or, in the case of carbonyl compounds showing low reactivity, the reduction reaction can hardly proceed even when the reaction temperature is raised.
The reduction of carbonyl compounds using DIBAH is a very useful method from the industrial viewpoint because of excellent reactivity and economics, among others. This method is in use, for example, for the reduction of .alpha.-aminochloroketone derivatives derived from leucine. When said .alpha.-aminochloroketone derivatives are reduced at -78.degree. C. using DIBAH, the erythro form can be obtained preferentially with an about 75% diastereomer excess [Tetrahedron Letters, 36, 5453 (1995)].
The term "erythro form" as used herein means an isomer in which the neighboring amino and hydroxyl groups show the following relative configuration: ##STR2##
However, this reduction method requires a very low temperature in order that the reactivity may be controlled. Furthermore, when the method is applied to the reduction of said .alpha.-aminochloroketone derivatives, it is impossible to attain such a high stereoselectivity as 90% or more as expressed in terms of diastereomer excess.
Referring to the reduction reaction of carbonyl compounds with diisobutylaluminum hydride, the literature suggests the possibility that the diisobutylaluminum alkoxides formed as reaction intermediates be partly involved in the reduction reaction [Journal of Organic Chemistry, 38, 4232 (1973)]. However, no reports have ever suggested that dialkylaluminum monoalkoxides such as diisobutylaluminum isopropoxide might be effective in the reduction or stereoselective reduction of carbonyl compounds. Likewise, no reports have ever suggested that reducing agents prepared from a dialkylaluminum hydride, such as diisobutylaluminum hydride, and an alcohol, such as isopropyl alcohol, might be effective in the reduction or stereoselective reduction of carbonyl compounds.
In view of the foregoing, it is an object of the present invention to provide a method of reducing carbonyl compounds to the corresponding hydroxyl compounds in an easy and simple manner and under milder conditions. Another object is to provide a method of reducing certain carbonyl compounds that can hardly be reduced with ordinary aluminum trialkoxides and, in particular, a method for stereoselectively reducing .alpha.-aminoketone derivatives.